Histidinol dehydrogenase [L-Histidinol-NAD Oxido-Reductase (EC 1.1.1.23)] catalyzes the final two steps in the biosynthesis of the amino acid histidine. This reaction is an oxidation of histidinol to histidinal to histidine, which is coupled to reduction of two moles of the required cofactor NAD per mole of histidine formed. EQU Histidinol+NAD+.fwdarw.Histidine+2 NADH
While the enzyme and gene encoding it have been well characterized in the bacteria Salmonella typhimurium [Yourno and Ino, J. Biol. Chem. 243:3273-3276 (1968); Gorisch and Holke, Eur. J. Biochem. 150:305-308 (1985); and Grubmeyer et al., Biochem. 28:8174-8180 (1989)] and Escherichia coli [Bitar et al., Biochem. Biophys. Acta 493:429-440 (1977)] and the yeast Saccharomyces cereviseae [Schaffer et al., Brookhaven Symp. Biol. 23:250-270 (1972); and Keesey et al., J. Biol. Chem. 254:7427-7433 (1979)], this enzyme has not been previously purified to homogeneity from any plant sources. This is in part because enzymes for primary metabolic functions such as amino acid biosynthesis are especially difficult to purify due to their low concentration in the source tissue. In plants, this difficulty is compounded by the existence of phenolic compounds and other secondary metabolites that can react with proteins throughout their purification.
Histidine biosynthesis in general in higher plants has not been studied well. Some evidence for the existence in plants of a biosynthetic pathway similar to that in microorganisms has been obtained from in vivo experiments using various different plants and a blue-green algae [Dougall and Fulton, Plant Physiol. 42:941-945 (1967); Negrutiu et al., Mol. Gen. Genet. 199:330-337 (1985); Helm et al., Plant Physiol. 91:1226-1231 (1989); Yavada, Mol. Gen. Genet. 170:109-111 (1979)].
Histidinol dehydrogenase activity has been detected in ten different plant species: asparagus, cabbage, cucumber, egg plant, lettuce, radish [Wong and Mazalis, Phytochrom. 20:1831-1834 (1981)], rose, squash [Wong and Mazalis, Phytochem. 20:1831-1834 (1981)], turnip [Wong and Mazalis, Phytochem. 20:1831-1834 (1981)], and wheat [Wong and Mazalis, Phytochem. 20:1831-1834 (1981) and this work] and in 5 preparations of distinct cell differentiation: germ [[Wong and Mazalis, Phytochrom. 20:1831-1834 (1981)] and this work), root [Wong and Mazalis, Phytochrom. 20:1831-1834 (1981)], fruit [Wong and Mazalis, Phytochrom. 20:1831-1834 (1981) and this work], shoot, and cultured cell.
Only a few attempts have been made to study the enzymes involved in histidine (His) biosynthesis in higher plants. The hitherto impossible task of purifying to homogeneity any histidine biosynthesis enzyme from plants seems to be the limiting step in biochemical investigations. In crude extracts from shoots of barley, oats and peas, the activities of ATP-phosphoribosyl transferase, imidazoleglycerol phosphate dehydratase and histidinol phosphate phosphatase were detected [Wiater et al., Acta Biochim. Polonica 18:299-307 (1971)]. Histidinol dehydrogenase activity has been found in crude extracts of different plant species [Wong et al., Phytochem. 20:1831-1834 (1981)]. These data suggest that histidine biosynthesis in plants follows the same pathway as in microorganisms, although no protein has ever been isolated from plants and identified as an enzyme involved directly in histidine biosynthesis.
The pathways for biosynthesis of the ten amino acids essential to the human diet are of special interest as targets for development of novel inhibitory compounds that could act as herbicides. This interest is due to the likelihood that a specific inhibitor of any enzyme from these pathways will be completely non-toxic to vertebrates, which lack the biosynthetic pathways for the essential amino acids.